Mp65-03 Immunoproteasome Acted as the Potential Candidate Markers for Immune Checkpoint Inhibitors Therapy in Solid Tumor: A Large Population High-Throughput Sequencing Study

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (MP65)1 May 2024MP65-03 IMMUNOPROTEASOME ACTED AS THE POTENTIAL CANDIDATE MARKERS FOR IMMUNE CHECKPOINT INHIBITORS THERAPY IN SOLID TUMOR: A LARGE POPULATION HIGH-THROUGHPUT SEQUENCING STUDY Yi Lu Yi LuYi Lu View All Author Informationhttps://doi.org/10.1097/01.JU.0001008756.24343.22.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immunoproteasome played crucial role in the process of endogenous antigenic peptides, including viral proteins and tumor antigens. It has been reported that a high level of immune proteasome content is associated with improved prognosis in a variety of tumors, and its effect on the efficacy of immune checkpoint inhibitors is still unclear. METHODS: In the present study, we focused on multi-omics regulatory mechanisms of the immunoproteasome in 33 cancers and 8947 tumor samples. Two single-cell sequencing cohorts, GSE84465 (3589 samples) and GSE72056 (4645 samples) were applied to illustrate the correlation between immunoproteasome and tumor antigen peptide. Two immune checkpoint therapy cohorts were downloaded from http://research-pub.gene.com/IMvigor210CoreBiologies (348 samples) and GEO (28 samples) database, which found immunoproteasome improve the clinical response to immune checkpoint therapy. RESULTS: Immunoproteasome content was higher in tumor tissues than in para-cancerous tissues, predicted outcomes of solid tumors, and was a risk factor in hematologic tumors. Increased immunoproteasome content is accompanied by increased CD8+T lymphocyte content in tissues. Immuneproteasome strongly positively correlated with immune checkpoints and HLA-family molecules based on the transcriptome and single-cell analysis. This finding suggests that the immunoproteasome may lead strong anti-tumor effect. Based on multi-omics studies, we found that the PSMB8 subunit is regulated by DNA methylation, and we identified 23 microRNAs that regulate immunoproteasome expression. Finally, we found that immunoproteasome can be used as the basis for immune checkpoint treatment. The proportion of complete responses to therapy was higher in patients with more immunoproteasomes than in those with fewer. CONCLUSIONS: Immunoproteasome promote the infiltration of CD8+T lymphocytes in the tumor microenvironment by affecting the synthesis of tumor antigen peptides, and improve the clinical response to immune checkpoint therapy. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1077 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yi Lu More articles by this author Expand All Advertisement PDF downloadLoading ...